Genomic Organization of Recombination Hot Spots

重组热点的基因组组织

• 批准号: 7333195
• 负责人: KENNETH PAIGEN
• 金额: $ 30.99万
• 依托单位: JACKSON LABORATORY
• 依托单位国家: 美国
• 财政年份: 2006
• 资助国家: 美国
• 起止时间: 2006-01-01 至 2009-12-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7333195
• 关键词: Accounting; Affect; Alleles; Bacteria; Bacteriophages; Biological; Biological Process; Burkitt Lymphoma; Characteristics; Chromatids; Chromosome Mapping; Chromosome Pairing; Chromosome Structures; Chromosomes; Complex; Congenic Mice; Congenic Strain; Consensus Sequence; DNA; DNA Sequence; Data; Detection; Distal; Distant; Elements; Family; Female; Frequencies; Funding; Gene Conversion; Genes; Genetic Recombination; Genetic Variation; Genetic screening method; Genome; Genomics; Goals; Guanine + Cytosine Composition; Haplotypes; Hot Spot; Human; Informatics; Knowledge; Linkage Disequilibrium; Location; Mammals; Maps; Matrix Attachment Regions; Meiosis; Molecular; Mus; Numbers; Organism; Plasmacytoma; Polymerase Chain Reaction; Process; Promoter Regions; Property; Proteins; Purpose; Relative (related person); Repetitive Sequence; Research; Residual state; Resolution; Role; Sampling; Site; Specificity; Synapses; System; Testing; Time; Vascular Plant; Virus; Yeasts; c-myc Genes; density; gene cloning; human disease; imprint; male; mouse genome; programs; research study; sex; sperm cell

Understanding the genomic distribution of mammalian recombination is a matter of considerable importance for 1) optimizing strategies for association studies mapping human disease genes by linkage disequilibrium, 2) optimizing experimental strategies for mapping and cloning genes in experimental mammals, 3) understandingthe role of recombinational hotspots in evolutionary processes, and 4) under- standing genetic recombination as a biological process. The purpose of the proposed research is to provide a molecular description of the locations and properties of hotspots in a sample of the mouse genome. We will map to a resolution of 1.5 Kb, the locations of 900-1000 crossovers occurring in five 5-megabase regions of the mouse genome, selected for specific characteristics. The crossovers, which we expect to describe nearly 80 recombinational hotspots, will be identified in DNAs from (C57BL/6J x CAST/EiJ) F2 progeny. Our hotspot characterizations will provide the locations and recombination frequencies of all hotspots down to a level of 0.02 cM/hotspot, and will include the haplotype and sex specificity of each hotspot. To our knowledge, this will be the first such large-scale effort for a mammal. Informatics studies will attempt to identify key hotspot sequences and chromosomal features that define hotspot locations. Additionally, for one of the chromosomal regions, we will carry out a genetic test for the existence of trans-acting genes required for hotspotactivity.

了解哺乳动物重组的基因组分布是一个相当重要的问题。 1)通过连锁定位人类疾病基因的关联研究的优化策略的重要性 不平衡，2)实验中基因定位和克隆的优化实验策略 哺乳动物，3)了解重组热点在进化过程中的作用，4)在- 将基因重组视为一个生物过程。 拟议研究的目的是提供位置和位置的分子描述 小鼠基因组样本中热点的性质。我们将映射到1.5KB的分辨率， 在小鼠基因组的五个5兆碱基区域中发生900-1000个交叉的位置，选择用于 特定的特征。我们预计将描述近80个重组热点的交叉， 将在(C57BL/6J x CAST/EIJ)F2后代的DNA中鉴定。我们的热点描述将会是 提供所有热点的位置和重组频率，最低可达0.02厘米/热点，以及 将包括每个热点的单倍型和性别特异性。据我们所知，这将是第一次 对于哺乳动物来说，这是一项大规模的努力。 信息学研究将试图识别关键的热点序列和染色体特征，这些特征定义了 热点位置。 此外，对于其中一个染色体区域，我们将进行基因测试，以确定是否存在 热点活动所需的反式作用基因。